Expression of stromal cell-derived factor 1 and CXCR7 ligand receptor system in pancreatic adenocarcinoma

World Journal of Surgical Oncology

Bao-Sheng Wang¹  Xiang-Peng Meng¹  Xu-Yong Teng¹  Zhen Liu¹ 

[1] Department of General Surgery, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Shenyang 110004, China

关键词: SDF-1;    pancreatic neoplasms;    CXCR7;    chemokine receptors;    chemokine;   

Others  :  1147255
DOI  :  10.1186/1477-7819-12-348

 received in 2014-02-01, accepted in 2014-10-03,  发布年份 2014

【 摘 要 】

Background

Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Research has demonstrated that SDF-1/CXCR7 interaction could play an important role in cancer progression. In this study, we aimed to investigate the expression of the SDF-1/CXCR7 ligand receptor system and the relationship between this expressions and clinicopathological characteristics in pancreatic adenocarcinoma.

Methods

Expressions of SDF-1 and CXCR7 in 64 cases of pancreatic adenocarcinoma tissue and 24 cases of normal pancreatic tissue were detected immunohistochemically.

Results

Expressions of SDF-1 and CXCR7 were negative in normal pancreatic tissues. Respectively, positive expression rates of SDF-1 and CXCR7 in pancreatic adenocarcinoma were 45.3% and 51.6%. The expression of SDF-1 correlated with histological grades; the expression rate in moderate to low differentiation was higher than in high differentiation (P <0.05). The expression of CXCR7 positively correlated with lymph node metastasis (P <0.05). A log-rank test showed that the expression of SDF-1⁺/CXCR7⁺ correlated with poor prognosis (P <0.05).

Conclusions

The SDF-1/CXCR7 receptor ligand system may take part in invasive progression and metastasis of pancreatic adenocarcinoma, and might be useful as an index for evaluating invasiveness and prognosis.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA: A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 1996, 184:1101-1109.
• [2]Ara T, Nakamura Y, Egawa T, Sugiyama T, Abe K, Kishimoto T, Matsui Y, Nagasawa T: Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1). Proc Natl Acad Sci USA 2003, 100:5319-5323.
• [3]Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS: Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 2003, 362:697-703.
• [4]Ma Q, Jones D, Borghesani PR, Nagasawa T, Kishimoto T, Bronson RT, Springer TA: Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 1998, 95:9448-9453.
• [5]Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC: The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997, 185:111-120.
• [6]Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T: Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996, 382:635-638.
• [7]Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A, Kleer CG, Essner JJ, Nasevicius A, Luker GD, Howard MC, Schall TJ: CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA 2007, 104:15735-15740.
• [8]Marchesi F, Monti P, Leone BE, Zerbi A, Vecchi A, Piemonti L, Mantovani A, Allavena P: Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Cancer Res 2004, 64:8420-8427.
• [9]Sutton A, Friand V, Brulé-Donneger S, Chaigneau T, Ziol M, Sainte-Catherine O, Poiré A, Saffar L, Kraemer M, Vassy J, Nahon P, Salzmann JL, Gattegno L, Charnaux N: Stromal cell-derived factor-1/chemokine (C-X-C motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion. Mol Cancer Res 2007, 5:21-33.
• [10]Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ: A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 2006, 203:2201-2213.
• [11]Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ, Mehra R, Loberg R, Taichman RS: The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 2008, 283:4283-4294.
• [12]Rot A, von Andrian UH: Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol 2004, 22:891-928.
• [13]Luther SA, Cyster JG: Chemokines as regulators of T cell differentiation. Nat Immunol 2001, 2:102-107.
• [14]Kulbe H, Levinson NR, Balkwill F, Wilson JL: The chemokine network in cancer - much more than directing cell movement. Int J Dev Biol 2004, 48:489-496.
• [15]Vicari AP, Caux C: Chemokines in cancer. Cytokine Growth Factor Rev 2002, 13:143-154.
• [16]Geminder H, Sagi-Assif O, Goldberg L, Meshel T, Rechavi G, Witz IP, Ben-Baruch A: A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma. J Immunol 2001, 167:4747-4757.
• [17]Kryczek I, Lange A, Mottram P, Alvarez X, Cheng P, Hogan M, Moons L, Wei S, Zou L, Machelon V, Emilie D, Terrassa M, Lackner A, Curiel TJ, Carmeliet P, Zou W: CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Res 2005, 65:465-472.
• [18]Meijer J, Ogink J, Roos E: Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo. Br J Cancer 2008, 99:1493-1501.
• [19]Zheng K, Li HY, Su XL, Wang XY, Tian T, Li F, Ren GS: Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells. J Exp Clin Cancer Res 2010, 29:31. BioMed Central Full Text
• [20]Schutyser E, Su Y, Yu Y, Gouwy M, Zaja-Milatovic S, Van Damme J, Richmond A: Hypoxia enhances CXCR4 expression in human microvascular endothelial cells and human melanoma cells. Eur Cytokine Netw 2007, 18:59-70.
• [21]Goldmann T, DrÖmann D, Radtke J, Marwitz S, Lang DS, Schultz H, Vollmer E: CXCR7 transcription in human non-small cell lung cancer and tumor-free lung tissues; possible regulation upon chemotherapy. Virchows Arch 2008, 452:347-348.
• [22]Maréchal R, Demetter P, Nagy N, Berton A, Decaestecker C, Polus M, Closset J, Devière J, Salmon I, Van Laethem JL: High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma. Br J Cancer 2009, 100:1444-1451.
• [23]Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, Makowiec F: The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg 2009, 13:1337-1344.
• [24]Fujita T, Nakagohri T, Gotohda N, Takahashi S, Konishi M, Kojima M, Kinoshita T: Evaluation of the prognostic factors and significance of lymph node status in invasive ductal carcinoma of the body or tail of the pancreas. Pancreas 2010, 39:48-54.